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Preparation method of cis-hexahydroisoindoline

A kind of hexahydroisoindole, cis technology

Inactive Publication Date: 2011-06-22
张家港田由新材料科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Catalytic hydrogenation of cis-tetrahydrophthalimide with Raney nickel requires a pressure of 12 MPa. The reaction conditions are demanding, difficult to operate, and the yield in the reduction process is low and the reduction is incomplete.

Method used

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  • Preparation method of cis-hexahydroisoindoline
  • Preparation method of cis-hexahydroisoindoline

Examples

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Embodiment 1

[0019] Step 1, the synthesis of cis-1,2,3,6-tetrahydrophthalic anhydride

[0020] Add maleic anhydride (98.0 g, 1.000 mol) into a reactor filled with dry benzene (250 mL), and feed 1,3-butadiene at a constant speed (0.6-0.8 L / min) under heating and stirring, and the reaction temperature After reaching 50 °C, heat for another 3 min, then stop heating, continue to feed 1,3-butadiene, react for 3.5 h, GC detects that the raw material maleic anhydride disappears, stop the reaction, stand at 0~5 °C for 12 h to crystallize , suction filtration, washing with petroleum ether, drying at ≤60 ℃ to constant weight, yield: 96.7%;

[0021] Step 2, the synthesis of cis-cyclohexanedicarboxylic anhydride

[0022] Dissolve cis-1,2,3,6-tetrahydrophthalic anhydride (178.3 g, 1.173 mol) in methanol (2000 mL), add 10% Pd / C (35.6 g), first vacuum, then use Replaced with hydrogen 3 times, introduced hydrogen, hydrogenated at normal pressure for 22 hours, filtered the reaction solution with suction,...

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Abstract

The invention discloses a preparation method of cis-hexahydroisoindoline, which comprises the following steps: enabling maleic anhydride and 1,3-butadiene, which are used as raw materials, to be subjected to Diels-Alder reaction to obtain cis-1,2,3,6-tetrahydrophthalic anhydride (I); carrying out Pb / C hydrogenation on the product I to obtain cis-cyclohexanedicarboxylic anhydride (II); reacting the product II with carbamide to obtain cis-hexahydrophthalimide (III); and reducing the product III with lithium aluminum hydride in anhydrous tetrahydrofuran to obtain the target product cis-hexahydroisoindoline. The Mitiglinide calcium preparation method disclosed by the invention can save the raw material cis-hexahydroisoindoline, and has high chiral degree of separation.

Description

technical field [0001] The invention relates to a preparation method of cis-hexahydroisoindole. Background technique [0002] Cis-hexahydroisoindole is an important intermediate of mitiglinide calcium, and its derivatives can also be used to prepare other medicines or agricultural chemical products. Cis-hexahydroisoindole generally uses maleic anhydride and 1,3-butadiene as raw materials, and adopts the classic Diels-Alder reaction to obtain cis-1,2,3 , 6-tetrahydrophthalic anhydride, and then react with ammonia gas to obtain cis-1,2,3,6-tetrahydrophthalimide, and then use Raney nickel to catalyze hydrogenation, first reduce benzene The olefinic bond on the ring and the carbonyl group on one of the amides, and the remaining carbonyl group are then reduced with lithium aluminum hydride. Catalytic hydrogenation of cis-tetrahydrophthalimide with Raney nickel requires a pressure of 12 MPa, which requires high reaction conditions and is not easy to operate. Moreover, the yield ...

Claims

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Application Information

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IPC IPC(8): C07D209/44
Inventor 刘林密
Owner 张家港田由新材料科技有限公司
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